tbuckley/cabot-search huggingface dataset:
Clinical benefit, development, innovation, trials, epidemiology, and price for cancer drugs and indications with multiple special FDA designations
Authors: Daniel Tobias Michaeli, Thomas Michaeli, Sebastian Albers, Julia Caroline Michaeli
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background This study analyzes the development, US Food and Drug Administration (FDA) approval, benefits, innovation, trials, epidemiology, and price of cancer drugs with multiple special designations: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. Methods In total, 355 FDA-approved cancer drug indications with 841 special designations were identified (2012-2022). Trial, epidemiology, and price data were collected from FDA labels, the Global Burden of Disease study, and Medicare and Medicaid. The association between efficacy outcomes and indications’ number of special designations were compared in meta-analyses. Results Median development times were 7.3, 7.8, and 5.4 months (P = .027) for drugs with 0 to 1, 2 to 3, and 4 to 5 special designations, respectively. Multiple special designations were associated with higher biotechnological and clinical innovation. Median patient enrollment in trials were 615, 471, 398, 168, 104, and 120 (P &amp;lt; .001) for indications with 0 to 5 special designations. Drugs for rare diseases supported by open-label phase 1/2 trials of single-arm design were granted more special designations. Hazard ratios for overall survival (0.80 vs 0.73 vs 0.73 vs 0.69 vs 0.56 vs 0.52; P = .003) and progression-free survival (0.70 vs 0.61 vs 0.59 vs 0.44 vs 0.37 vs 0.67; P &amp;lt; .001) substantially declined while tumor response increased with more special designations. Mean monthly prices increased for drugs with 0 to 4 but not 5 special designations ($21 596 vs $14 753 vs $32 410 vs $41 240 vs $38 703 vs $19 184). Conclusions Multiple special designations are associated with faster clinical development and greater benefits for patients with unmet needs but also with nonrobust trial evidence and a tendency toward higher drug prices.
Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Authors: Alexandra Schnell, Linglin Huang, Brianna M. L. Regan, Vasundhara Singh, Dominik Vonficht, Alina Bollhagen, Mona Wang, Yu Hou, Lloyd Bod, Raymond A. Sobel, Norio Chihara, Asaf Madi, Ana C. Anderson, Aviv Regev, Vijay K. Kuchroo
Journal: Nature Immunology (2023)
High Influenza Incidence and Disease Severity Among Children and Adolescents Aged &lt;18 Years ― United States, 2022–23 Season
Authors: Elizabeth B. White, Alissa O’Halloran, Devi Sundaresan, Matthew Gilmer, Ryan Threlkel, Arielle Colón, Katie Tastad, Shua J. Chai, Nisha B. Alden, Kimberly Yousey-Hindes, Kyle P. Openo, Patricia A. Ryan, Sue Kim, Ruth Lynfield, Nancy Spina, Brenda L. Tesini, Marc Martinez, Zachary Schmidt, Melissa Sutton, H. Keipp Talbot, Mary Hill, Matthew Biggerstaff, Alicia Budd, Shikha Garg, Carrie Reed, A. Danielle Iuliano, Catherine H. Bozio
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October.
Correction:<i>Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study</i>
Journal: Annals of the Rheumatic Diseases (2023)

In discussion on page 187, the following sentence does not contain the final results: "Our results for subgroups of patients with at least one cardiovascular risk who were 50 years old or older and 65 years old or older were not significant for risk of both MACEs and VTEs with a JAKi compared with the TNFi adalimumab: HRw 2.1 (0.6 to 7.8) and 2.2 (0.4 to 12.5) and 1.1 (0.5 to 2.2) and 0.8 (0.4 to 2.0), respectively."This should read: "Our results for subgroups of patients with at least one cardiovascular risk who were 50 years old or older and 65 years old or older were not significant for risk of both MACEs and VTEs with a JAKi compared with the TNFi adalimumab: HRw 1.0 (0.6 to 1.9) and 0.7 (0.4 to 1.3) and 1.5 (0.8 to 2.6) and 1.2 (0.6 to 2.3), respectively."
Clinically informed machine learning elucidates the shape of hospice racial disparities within hospitals
Authors: Inas S. Khayal, A. James O’Malley, Amber E. Barnato
Journal: npj Digital Medicine (2023)

Abstract Racial disparities in hospice care are well documented for patients with cancer, but the existence, direction, and extent of disparity findings are contradictory across the literature. Current methods to identify racial disparities aggregate data to produce single-value quality measures that exclude important patient quality elements and, consequently, lack information to identify actionable equity improvement insights. Our goal was to develop an explainable machine learning approach that elucidates healthcare disparities and provides more actionable quality improvement information. We infused clinical information with engineering systems modeling and data science to develop a time-by-utilization profile per patient group at each hospital using US Medicare hospice utilization data for a cohort of patients with advanced (poor-prognosis) cancer that died April-December 2016. We calculated the difference between group profiles for people of color and white people to identify racial disparity signatures. Using machine learning, we clustered racial disparity signatures across hospitals and compared these clusters to classic quality measures and hospital characteristics. With 45,125 patients across 362 hospitals, we identified 7 clusters; 4 clusters ( n = 190 hospitals) showed more hospice utilization by people of color than white people, 2 clusters ( n = 106) showed more hospice utilization by white people than people of color, and 1 cluster ( n = 66) showed no difference. Within-hospital racial disparity behaviors cannot be predicted from quality measures, showing how the true shape of disparities can be distorted through the lens of quality measures. This approach elucidates the shape of hospice racial disparities algorithmically from the same data used to calculate quality measures.
The airway smooth muscle layer is structurally abnormal in low birth weight infants: implications for obstructive disease
Authors: Kimberley C.W. Wang, John G. Elliot, Sejal Saglani, Graham M. Donovan, Alan L. James, Peter B. Noble
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Low birth weight infants born at term have structurally abnormal airway smooth muscle which may contribute to an increased risk of obstructive disease</b> https://bit.ly/3F0GmOd
Rethinking placebos: embracing synthetic control arms in clinical trials for rare tumors
Authors: César Serrano, Sara Rothschild, Guillermo Villacampa, Michael C. Heinrich, Suzanne George, Jean-Yves Blay, Jason K. Sicklick, Gary K. Schwartz, Sameer Rastogi, Robin L. Jones, Piotr Rutkowski, Neeta Somaiah, Víctor Navarro, Denisse Evans, Jonathan C. Trent
Journal: Nature Medicine (2023)
Hypertriglyceridemia in Apoa5–/– mice results from reduced amounts of lipoprotein lipase in the capillary lumen
Authors: Ye Yang, Anne P. Beigneux, Wenxin Song, Le Phuong Nguyen, Hyesoo Jung, Yiping Tu, Thomas A. Weston, Caitlyn M. Tran, Katherine Xie, Rachel G. Yu, Anh P. Tran, Kazuya Miyashita, Katsuyuki Nakajima, Masami Murakami, Yan Q. Chen, Eugene Y. Zhen, Joonyoung R. Kim, Paul H. Kim, Gabriel Birrane, Peter Tontonoz, Michael Ploug, Robert J. Konrad, Loren G. Fong, Stephen G. Young
Journal: Journal of Clinical Investigation (2023)

Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we suspected that the underlying cause was reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5–/– mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific monoclonal antibodies, the binding of LPL antibodies to heart and BAT capillaries (relative to CD31 or GPIHBP1 antibodies) was reduced in Apoa5–/– mice. LPL levels in the postheparin plasma were also lower in Apoa5–/– mice. We suspected that a recent biochemical observation—that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity—could be related to the low intracapillary LPL levels in Apoa5–/– mice. We showed that an ANGPTL3/8-specific monoclonal antibody (IBA490) and APOA5 normalize plasma triglyceride levels and intracapillary LPL levels in Apoa5–/– mice. We also showed that ANGPTL3/8 detaches LPL from HSPGs and GPIHBP1 on the surface of cells and that the LPL detachment is blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5–/– mice and further illuminate the molecular mechanisms that regulate plasma triglyceride metabolism.
Receptor-interacting Protein Kinase 2 Is an Immunotherapy Target in Pancreatic Cancer
Authors: Wenhua Sang, Yiduo Zhou, Haiyan Chen, Chengxuan Yu, Lisi Dai, Zhongkun Liu, Lang Chen, Yimin Fang, Panpan Ma, Xiangji Wu, Hao Kong, Wenting Liao, Hong Jiang, Junbin Qian, Da Wang, Yun-Hua Liu
Journal: Cancer Discovery (2023)

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy because of its aggressive nature and the paucity of effective treatment options. Almost all registered drugs have proven ineffective in addressing the needs of patients with PDAC. This is the result of a poor understanding of the unique tumor-immune microenvironment (TME) in PDAC. To identify druggable regulators of immunosuppressive TME, we performed a kinome- and membranome-focused CRISPR screening using orthotopic PDAC models. Our data showed that receptor-interacting protein kinase 2 (RIPK2) is a crucial driver of immune evasion of cytotoxic T-cell killing and that genetic or pharmacologic targeting of RIPK2 sensitizes PDAC to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy, leading to prolonged survival or complete regression. Mechanistic studies revealed that tumor-intrinsic RIPK2 ablation disrupts desmoplastic TME and restores MHC class I (MHC-I) surface levels through eliminating NBR1-mediated autophagy-lysosomal degradation. Our results provide a rationale for a novel combination therapy consisting of RIPK2 inhibition and anti-PD-1 immunotherapy for PDAC. PDAC is resistant to almost all available therapies, including immune checkpoint blockade. Through in vivo CRISPR screen, we identified that RIPK2 plays a crucial role in facilitating immune evasion by impeding antigen presentation and cytotoxic T-cell killing. Targeting tumor-intrinsic RIPK2 either genetically or pharmacologically improves PDAC to anti-PD-1 immunotherapy. See related commentary by Liu et al., p. 208 . This article is featured in Selected Articles from This Issue, p. 201.
Cryptic MHC-E epitope from influenza elicits a potent cytolytic T cell response
Authors: Michael J. Hogan, Nikita Maheshwari, Bridget E. Begg, Annalisa Nicastri, Emma J. Hedgepeth, Hiromi Muramatsu, Norbert Pardi, Michael A. Miller, Shanelle P. Reilly, Laurent Brossay, Kristen W. Lynch, Nicola Ternette, Laurence C. Eisenlohr
Journal: Nature Immunology (2023)
Correction:<i>Points to consider: EULAR–UEMS standards for the training of European rheumatologists</i>
Authors: Alessia Alunno, Tadej Avčin, Catherine Haines, Sofia Ramiro, Francisca Sivera, Sara Badreh, Xenofon Baraliakos, Johannes Wj Bijlsma, Frank Buttgereit, Kaushik Chaud- Huri, Jose Antonio, P Da Silva, Jean Dudler, Ricardo Ferreira, Tania Gudu, Eric Hachulla, Mette Holland-Fischer, Annamaria Iagnocco, Tue Kragstrup, Gyorgy Nagy, Vasco Romão, Simon Stones, Marloes Van Onna, Chris- Topher Edwards
Journal: Annals of the Rheumatic Diseases (2023)
“Coming Full Circle”: Reintroduction of Radiotherapy Delaying Chemotherapy Followed by Craniospinal Radiotherapy for Infants With Medulloblastoma
Authors: Nicholas G. Gottardo
Journal: Journal of the National Comprehensive Cancer Network (2023)

"“Coming Full Circle”: Reintroduction of Radiotherapy Delaying Chemotherapy Followed by Craniospinal Radiotherapy for Infants With Medulloblastoma" published on Oct 2023 by National Comprehensive Cancer Network.
Prevalence of <i>Acinetobacter baumannii</i> and <i>Candida auris </i>in Patients Receiving Mechanical Ventilation
Authors: Anthony D. Harris, Lisa Pineles, J. Kristie Johnson, Lyndsay M. O’Hara, L. Leigh Smith, Indira French, Jamie Rubin, Rebecca Perlmutter, Ashley Heller, Liore Klein, John Thoguru, David Blythe, Elisabeth Vaeth
Journal: JAMA (2023)

To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown.
Pleural Cryoglobulins
Authors: Mehtap Ünal, Yvette A de Reus, Koos J.G. van de Belt, L. Joost van Pelt, Abraham Rutgers
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

A 63-year-old woman with a medical history of hepatitis C-negative mixed essential cryoglobulinemia presented with thoracic pain and dyspnea.Initial analysis showed no cardiac ischemia or pulmonary embolism.Bilateral pleural effusion developed 1 week later (Figure 1), with weight gain and purpura observed.Echocardiography showed normal left and right ventricle function with a collapsing inferior vena cava, making heart failure unlikely.Thoracocentesis yielded a rapidly clotting, clear yellow transudate Figure 1.(A and B) Bilateral pleural fluid on chest radiograph.(C and D) Rapidly clotting pleural fluid obtained via thoracocentesis.
Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs
Authors: Vivek Narayan, Tao Liu, Yunjie Song, Joshua Mitchell, JoRean Sicks, Ilana Gareen, Lova Sun, Srinivas Denduluri, Ciaran Fisher, Jesse Manikowski, Mark Wojtowicz, Joseph Vadakara, Naomi Haas, Kenneth B. Margulies, Bonnie Ky
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied. Methods: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation. Results: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant “on-treatment” hypertension was not associated with MACE. Conclusions: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI–related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.
Benralizumab Normalizes Sputum Eosinophilia in Severe Asthma Uncontrolled by Anti–IL-5 Antibodies: A Single-Blind, Placebo-controlled Clinical Trial
Authors: Manali Mukherjee, Chynna Huang, Carmen Venegas-Garrido, Kayla Zhang, Anurag Bhalla, Xiaotian Ju, Paul M. O’Byrne, Sarah Svenningsen, Roma Sehmi, Parameswaran Nair
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Benralizumab Normalizes Sputum Eosinophilia in Severe Asthma Uncontrolled by Anti–IL-5 Antibodies: A Single-Blind, Placebo-controlled Clinical Trial." American Journal of Respiratory and Critical Care Medicine, 208(12), pp. 1330–1335
Changes in Prognostic Beliefs of Patients With Metastatic Cancer and Their Association With Changing Health Status
Authors: Isabella Gupta, Eric Andrew Finkelstein, Semra Ozdemir, Chetna Malhotra
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Patients’ prognostic beliefs are known to influence treatment decisions. However, the evolution of these beliefs over an extended period in patients with metastatic cancer is understudied. We assessed longitudinal changes in prognostic beliefs and investigated their association with patients’ changing health status. Methods: We surveyed a cohort of 600 patients with solid metastatic cancer every 9 months, up to 54 months. At each time point, we assessed whether patients believed their current treatments would cure them (responses classified as accurate, inaccurate, or uncertain belief) and tested the association of their response with symptom burden and recent unplanned hospital admission. Results: Only 29% of patients had accurate prognostic belief at baseline, and 24% of patients changed from having accurate to uncertain/inaccurate belief at some point during follow-up. Patients who experienced greater symptom burden were less likely to report inaccurate (relative risk ratio [RRR], 0.87; 95% CI, 0.84–0.90) or uncertain prognostic belief (RRR, 0.90; 95% CI, 0.87–0.92), whereas those with a recent unplanned hospital admission were more likely to report inaccurate (RRR, 2.71; 95% CI, 1.48–4.94) or uncertain belief (RRR, 2.34; 95% CI, 1.34–4.07) compared with accurate belief. An increase in symptom burden was associated with change toward accurate belief (RRR, 1.75; 95% CI, 1.33–2.31) as opposed to no change. Conclusions: In our study of long-term changes in prognostic beliefs among patients with metastatic cancer, reported prognostic beliefs were unstable, changed from accurate to inaccurate/uncertain and vice versa, and were associated with their changing health status. Our findings imply that conversations about goals of care must occur regularly to factor in these changes.
Cutting-edge novel device in the treatment of obesity
Authors: Jan Kral, Jana Selucka, Katerina Waloszkova, Marek Buzga, Julius Spicak, Evzen Machytka
Journal: Endoscopy (2023)

A 57-year-old patient with arterial hypertension, dyslipidemia, and obesity grade I (BMI 34.9 kg/m2, 95 kg, 165 cm) underwent a new and unique sleeve gastroplasty procedure for weight reduction ([Video 1]).
Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology
Authors: Edward M. Schaeffer, Sandy Srinivas, Nabil Adra, Yi An, Daniel Barocas, Rhonda Bitting, Alan Bryce, Brian Chapin, Heather H. Cheng, Anthony Victor D’Amico, Neil Desai, Tanya Dorff, James A. Eastham, Thomas A. Farrington, Xin Gao, Shilpa Gupta, Thomas Guzzo, Joseph E. Ippolito, Michael R. Kuettel, Joshua M. Lang, Tamara Lotan, Rana R. McKay, Todd Morgan, George Netto, Julio M. Pow-Sang, Robert Reiter, Mack Roach, Tyler Robin, Stan Rosenfeld, Ahmad Shabsigh, Daniel Spratt, Benjamin A. Teply, Jonathan Tward, Richard Valicenti, Jessica Karen Wong, Dorothy A. Shead, Jenna Snedeker, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.
Chronic active Epstein-Barr virus disease originates from infected hematopoietic stem cells
Authors: Jingshi Wang, Min Su, Na Wei, Huanyu Yan, Jia Zhang, Yi Gong, Lin Wu, Dina Suolitiken, Yubo Pi, Deli Song, Leilei Chen, Huan Liu, Shuo Yang, Xi Wang, Zhao Wang
Journal: Blood (2023)
Letter to the Editor Re: Influence of Food With Different Fat Concentrations on Alectinib Exposure: A Randomized Crossover Pharmacokinetic Trial
Authors: Andrew D. Frugé, Kristen S. Smith, Sylvia L. Crowder, Wendy Demark-Wahnefried
Journal: Journal of the National Comprehensive Cancer Network (2023)

"Letter to the Editor Re: Influence of Food With Different Fat Concentrations on Alectinib Exposure: A Randomized Crossover Pharmacokinetic Trial" published on Oct 2023 by National Comprehensive Cancer Network.